Disturbances in the control of capillary flow in an aged APP(swe)/PS1 Delta E9 model of Alzheimer's disease

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Vascular changes are thought to contribute to the development of Alzheimer's disease, and both cerebral blood flow and its responses during neural activation are reduced before Alzheimer's disease symptoms onset. One hypothetical explanation is that capillary dysfunction reduces oxygen extraction efficacy. This study compares the morphology and hemodynamics of the microvasculature in the somatosensory cortex of 18-month-old APP(SWE)/PS1 Delta E9 (transgenic [Tg]) mice and wild-type (WT) littermates. In particular, the extent to which their capillary transit times homogenize during functional activation was measured and compared. Capillary length density was similar in both groups but capillary blood flow during rest was lower in the Tg mice, indicating that cortical oxygen availability is reduced. The capillary hemodynamic response to functional activation was larger, and lasted longer in Tg mice than in WT mice. The homogenization of capillary transit times during functional activation, which we previously demonstrated in young mice, was absent in the Tg mice. This study demonstrates that both neurovascular coupling and capillary function are profoundly disturbed in aged Tg and WT mice. (C) 2017 Elsevier Inc. All rights reserved.

Original languageEnglish
JournalNeurobiology of Aging
Volume62
Pages (from-to)82-94
Number of pages13
ISSN0197-4580
DOIs
Publication statusPublished - Feb 2018

    Research areas

  • Alzheimer's disease, Capillary dysfunction, Cerebral blood flow, Capillary transit time heterogeneity, Capillary length density, Red blood cell velocity, CEREBRAL-BLOOD-FLOW, TRANSIT-TIME HETEROGENEITY, APPSWE/PS1DE9 MOUSE MODEL, AMYLOID DEPOSITION, BRAIN-BARRIER, RODENT BRAIN, RAT, MICE, ACCUMULATION, METABOLISM

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